Article (Scientific journals)
Low daunomycin concentrations protect colorectal cancer cells from hypoxia-induced apoptosis
Lechanteur, Chantal; Jacobs, Nathalie; Greimers, Roland et al.
2005In Oncogene, 24 (10), p. 1788-1793
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Keywords :
hypoxia; apoptosis; daunomycin; colorectal cancer; Akt; Bad
Abstract :
[en] Hypoxia, a common feature of solid tumors, is a direct stress that triggers apoptosis in many cell types. Poor or irregular tumor vascularization also leads to a decreased drug diffusion and cancer cells distant from blood vessels (hypoxic cells) are exposed to low drug concentrations. In this report, we show that low daunomycin concentrations protect HCT116 colorectal cancer cells from hypoxia-induced apoptosis. While hypoxia induced p53 accumulation without expression of its responsive genes (bax and p21), daunomycin treatment restored p53 transactivation activity and cell cycle progression. We also demonstrated a role for Akt activation in daunomycin-induced protection through phosphorylation and inactivation of the Bcl-2 family proapoptotic factor Bad. Our data therefore suggest that chemotherapy could possibly, because of low concentrations in poorly vascularized tumors, protect cancer cells from hypoxia-induced cytotoxicity.
Research center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Oncology
Author, co-author :
Lechanteur, Chantal ;  Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Jacobs, Nathalie  ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Greimers, Roland ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Benoit, Valérie
Deregowski, Valérie
Chariot, Alain ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Merville, Marie-Paule ;  Université de Liège - ULiège > Département de pharmacie > Chimie médicale
Bours, Vincent ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique générale et humaine
Language :
English
Title :
Low daunomycin concentrations protect colorectal cancer cells from hypoxia-induced apoptosis
Publication date :
03 March 2005
Journal title :
Oncogene
ISSN :
0950-9232
eISSN :
1476-5594
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
24
Issue :
10
Pages :
1788-1793
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FNRS, TELEVIE, ARC ULG
Available on ORBi :
since 01 December 2008

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